The content of low-density lipoproteins (LDL) in human blood plasma is positively and that of high-density lipoproteins (HDL) negatively correlated with the risk of cardiac infarcation. Malchesky et al. (U.S. Pat. No. 4,350,156 and EP-A 0041350) therefore suggest that patients suffering from hypercholesteremia be treated using plasmapheresis. They provide thereby that the blood components containing cholesterol be rendered separable by means of suitable measures, e.g. the addition of heparin, and be separated by filtration from the blood plasma.
Seidel et al. have used an elegant method for this according to DE-OS 31 35 814. Their method is capable of holding HDL in the plasma and of separating LDL together with the fibrinogen which is pathologically elevated to an excess degree in patients at risk of cardiac infarction. They make use of the fact in this connection that HDL and LDL differ both in their molecular weights and also in their HLB (hydrophilic-lipophilic balance) (A. K. J. Koumans, A. P. Wildschut, "Nutrition and Atherosclerosis: Some Neglected Aspects", Clin. Cardiol 8, 1985, p. 549).
______________________________________ HDL LDL ______________________________________ Molecular weight (Dalton) approx. approx. 400,000 2-3.5 mio portion of cholesterol (%) i.e. hydrophobic = lipophilic 25 47 Protein (%) 22 25 hydrophilic 75 53 Lecithin (%) 53 28 ______________________________________
In this method, the blood plasma gained by plasmapheresis is diluted and lowered in pH. This gives the lipoproteins such as fibrinogen positive excess charges which complex with the heparin added in the buffer as polyanion. LDL precipitates as complex with a high hydrophobic portion whose lardaceous nature is unfavorable for filtering. For this reason, Rosskopf et al. suggest in DE-OS 33 10 727 for its separation a pressureless cross-flow filtration with the aid of a large-area filter cartridge in which a polycarbonate membrane is used. Almost two m.sup.2 membranes are used for this filter in application because a large part of the area is blocked by the precipitate.
From a medical standpoint, the large dead volume associated with this filter design is a disadvantage. In spite of the plasma being diluted with acetate buffer, a large volume of plasma ia removed from the body which must be returned to the greatest extent possible at the end of the treatment.
An urgent requirement of the described method is the necessity of removing the excess heparin from the blood plasma again in which the precipitation was performed. It is held fast in the methods according to DE-OS 18 35 814, Seidel et al. in an adsorption column to an anion exchanger. Then, the purified plasma, corrected in pH and in volume, is returned to the patient together with the cellular blood components.
The invention is therefore based on the designing of an efficient filter for separating the heparin complexes of pathological plasma components. A high performance density, that is, small volume, is intended to minimize the extracorporeal plasma volume and nevertheless achieve the required capacities. A additional problem is to unite the separation of precipitate and the separation of the heparin excess in one process in the multi-stage method according to the state of the art, e.g. according to DE-OS 31 35 814.